Gastrointestinal drugs Department of Pharmacology Tang Huifang (汤慧芳) Email: tanghuifang@zju.edu.cn

Content Part 1. Drugs used for peptic ulcers Part 2. Modulators of gastroenteric functions

Peptic ulcers and treatment Part 1. Drugs used for peptic ulcers Peptic ulcers and treatment Pathogenesis of peptic ulcers Infection with Hp ; Increased gastric acid secretion; Inadequate mucosal defense to gastric acid. Treatment approaches Eradicating Hp ; Neutralizing gastric acid, or reducing secretion of the acid; Protecting the gastric mucosa from damage.

Drugs used for peptic ulcers Classifiction of anti-ulcer drugs I. Antacids: neutralizing the acid II. Drugs suppressing gastric acid secretion ①Muscarinic receptor antagonists ②H2 receptor antagonists ③Gastrin receptor antagonists ④ H+-K+-ATPase inhibitors (proton pump inhibitors) III. Antimicrobial drugs (Helicobacter pylori) IV. Mucosal protective drugs

Drugs used for peptic ulcers Ⅰ. Antacids(抗酸药) Basic substances that can reduce gastric acidity by neutralizing HCl; Drugs most in use: Aluminium hydroxide(氢氧化铝), Magnesium hydroxide(氢氧化镁), Magnesium trisilicate(三硅酸镁), Magnesium oxide(氧化镁), etc. Composition resparation, such as: Tab aluminium hydroxide compound(复方氢氧化铝片, 胃舒平), etc.

Drugs used for peptic ulcers (1) Antacids 1. Pharmacological effect Neutralizing gastric acid, diminish gastric acidity and inactivate pepsin（胃蛋白酶）activity 2. Clinical uses Used for peptic ulcer and acid-hypersecretory conditions.

Drugs used for peptic ulcers 3. Adverse effects (1) Constipation and stomach cramp (salt of aluminum) (2) Diarrhea (salt of magnesium) (3) Hypercalcium which can cause renal failure (Calcium) (4) Hypernatremia (sodium-containing antacids) 4. Drug interactions Avoid concurrent administration of antacids and a variety of drugs . (1) Affect rates of dissolution and absorption, bioavailbility, and renal elimination of many drugs (2) By binding to drugs (for example, tetracycline四环素), form insoluble complexes that are not absorbed

Drugs used for peptic ulcers Adminstration and dosage (1) Take antacids 1 h and 3 h after meals Seven times a day after meals and at bedtime. (2) Should not be taken continuously for more than 3 m for ulcer (3) To help avoid or reduce drug interaction, other medication should not be taken within 1-2 hours of taking an antacids

Drugs used for peptic ulcers Ⅱ. Drugs inhibiting gastric acid secretion ①Muscarinic receptor antagonists ②H2 receptor antagonists ③Gastrin receptor antagonists ④ H+-K+-ATPase inhibitors (proton pump inhibitors)

atropine misoprostol atropine Sucralfate carbonoxolone

A. Muscarinic receptor antagonists (M receptor blocker): Drugs most in use: Atropine(阿托品) Propantheline bromide(溴丙胺太林) Pirenzepine(哌仑西平) Telenzepine(替仑西平)

Atropine(阿托品) Drugs used for peptic ulcers Non-selective M receptor blocker: Block M1, M2, M3, M4, and M5 receptors. Block M3 receptor in Parietal cells( 壁细胞) Block M1 receptor in ganglion Block M receptors in ECL and G cells.

Drugs used for peptic ulcers Pirenzepine(哌仑西平) Selective M receptor blocker: Only block M1 and M2-receptors.

misoprostol Sucralfate carbonoxolone

Drugs used for peptic ulcers 1. Pharmacological effects high affinity for M1- and low affinity for M2-receptors of the smooth muscle of the ileum and urinary bladder. blocking of M1-muscarinic receptors in autonomic ganglia, inhibiting the secretion of HCl. 2. Clinical uses: peptic ulcers 3. Adverse effects Atropine-like effects, at larger doses. Telenzepine(替仑西平)

Drugs used for peptic ulcers B. H2 receptor antagonists: (西咪替丁) (雷尼替丁)

misoprostol Sucralfate carbonoxolone

Drugs used for peptic ulcers Cimetidine(西咪替丁) 1. Pharmacological effects Blocking H2 receptors, decreasing H+ secretion 2. Clinical uses (1) Duodenal and gastric ulcer: —— relieving symptoms, promoting healing of ulcers, and preventing ulcers. (2) Zollinger-Ellison syndrome (3) Reflux esophagitis; (4) Acute stress ulcers, etc.

Drugs used for peptic ulcers 3. Adverse effects (1)Side effects: constipation, diarhoea, tiredness, muscular pain, etc. (2)CNS effects: headache, dizziness, hal-lucination, etc. (elderly, long-term uses) (3)Endocretion effects: antiandrogen, gynecomastia(男性乳房发育), galactorrh-ea(溢乳), reduced sperm count, and male sexual dysfunction 4. Drug interactions Inhibiting hepatic P450: raising plasma concentrations of warfarin, phenytoin, diazepam, propranolol, quinidine and theophylline, etc.

Drugs used for peptic ulcers

5. Elimination Drugs used for peptic ulcers Urinary excretion is the principal route of elimination of cimetidine, the dose should be modified in patients with renal impairment.

Other H2 receptor antagonists: Drugs used for peptic ulcers Other H2 receptor antagonists: Ranitidine(雷尼替丁) Similar to cimetidine, but 5～10 times more potent, longer acting; Minimal side effects, no antiandrogenic and prolactin-stimulating effects, less inhibiting P450. Famotidine(法莫替丁) Similar to ranitidine, but 4～8 times more potent. Nizatidine(尼扎替丁) The potent is similar to ranitidine. Bioavailability is near 100%, principally eliminated by kidney

4 种H2-受体阻断药的比较 Drugs used for peptic ulcers 西咪替丁 2 1 400mg, bid 1   西咪替丁 2 1 400mg, bid 1 雷尼替丁 2-3 5-10 150mg, bid 0.1 法莫替丁 2.5-4 40 20mg, bid 0 尼扎替丁 2 5-10 150mg, bid 0 相对抑 酸活力 对肝药 酶抑制 药 名 剂　量 t1/2(h)

Omeprazole(奥美拉唑) Drugs used for peptic ulcers C. H+-K+-ATPase inhibitors (proton pump inhibitors) Omeprazole(奥美拉唑)

Drugs used for peptic ulcers Omepranzole × (the proton pump) Proton pump inhibitors are administered as inactive prodrugs. Within the acidified compartment the prodrug rapidly becomes protonated and is concentrated > 1000-fold within the parietal cell canaliculus. There, it rapidly undergoes a molecular conversion to the active, reactive thiophilic sulfonamide cation. The sulfonamide reacts with the H+/K+ ATPase, forms a covalent disulfide linkage, and irreversibly inactivates the enzyme

影响药物分布 药物的理化性质； 局部的血流量； 体液的pH值； 生物屏障(血脑屏障、胎盘屏障)等。 Drugs used for peptic ulcers 影响药物分布 药物的理化性质； 局部的血流量； 体液的pH值； 生物屏障(血脑屏障、胎盘屏障)等。 质子泵的分子构型

Drugs used for peptic ulcers 1. Pharmacological effects (1)Inhibiting gastric acid secretion by various stimuli(such as: histamine, gastrin, aspirin, ethanol, stress, etc.) (2)Inhibiting Hp . (3) protection for gastric mucosa 2. Clinical uses (1)Highly effective for duodenal and gas-tric ulcer: relieving symptoms, and promoting healing of ulcers Used with antimicrobial agents to eradicate Hp . (2)Reflux esophagitis; (3)Zollinger-Ellison syndrome

Drugs used for peptic ulcers 3. Adverse effects (1)Side effects: Less, such as: nausea, headache, diarrhoea, constipation and rash occur. (2)Increase of gastric carcinoid tumor (3)Others: hypersensitivity, gynecomastia(男性乳房发育) 4. Drug interactions Inhibiting hepatic P450, raising plasma concentrations of warfarin, phenytoin, diazepam, etc.

Drugs used for peptic ulcers Others Lansoprazole(兰索拉唑) Pantoprazole(泮他拉唑) Rebeprazole(雷贝拉唑)

Metabolism of the five proton pump inhibitors. Silvia Marelli & Fabio Pace (2012) Rabeprazole for the treatment of acidrelated disorders, Expert Review of Gastroenterology & Hepatology, 6:4, 423-435 The darker arrows indicate the pathways that contribute more.

Comparison of the mean values for area under the plasma concentration–time curve after one oral dose of omeprazole, rabeprazole, lansoprazole and pantoprazole in extensive metabolizers versus poor metabolizers. AUC: Area under the curve. Silvia Marelli & Fabio Pace (2012) Rabeprazole for the treatment of acidrelated disorders, Expert Review of Gastroenterology & Hepatology, 6:4, 423-435

Relative potencies of the five proton pump inhibitors based on a meta‑analysis of 57 studies measuring the mean 24-h gastric pH. Silvia Marelli & Fabio Pace (2012) Rabeprazole for the treatment of acidrelated disorders, Expert Review of Gastroenterology & Hepatology, 6:4, 423-435

Rebeprazole(雷贝拉唑) Silvia Marelli & Fabio Pace (2012) Rabeprazole for the treatment of acidrelated disorders, Expert Review of Gastroenterology & Hepatology, 6:4, 423-435

Key issues Rabeprazole is a more rapid and potent inhibitor of the gastric pump than other proton pump inhibitors. Clinical studies of rabeprazole show rapid onset of action, with faster symptom relief, even on the first day of therapy. Rabeprazole is safe and well tolerated, and due to its peculiar metabolism, reduced risks of drug–drug interactions are expected. In long-term maintenance therapy, rabeprazole is suitable for on-demand modality. Rabeprazole has shown clinical advantages in some subsets of gastroesophageal reflux disease patients, that is, polymedicated and overweight/obese subjects.

影响药物分布 药物的理化性质； 局部的血流量； 体液的pH值； 生物屏障(血脑屏障、胎盘屏障)等。 Drugs used for peptic ulcers 影响药物分布 药物的理化性质； 局部的血流量； 体液的pH值； 生物屏障(血脑屏障、胎盘屏障)等。 t1/2 有效抑酸 剂量 对肝药 (h) 时间(h) (mg/d) 酶影响 奥美拉唑 1.0 12～24 20～40 + 兰索拉唑 1.5 24 30  潘托拉唑 1.3 24 20～40  雷贝拉唑 1.0 24 20  几种质子泵抑制剂的比较 药　名

胃泌素受体阻断药: 丙谷胺(Proglumide) 　 本品可与胃泌素竞争受体而抑制胃酸分泌; 也能促进黏液合成, 增强胃黏膜的黏液-HCO3- 盐屏障, 从而发挥抗溃疡病的作用. 本品口服吸收迅速, 生物利用度为60%～74%, 达峰时间为2h.

Drugs used for peptic ulcers Ⅲ. Mucosal protective drugs Misoprostol(米索前列醇) Enprostil 恩前列素 Sucralfate 硫糖铝 Colloidal bismuth subcitrate(CBS, 胶体次枸橼酸铋) Teprenone(替普瑞酮) Marzulene(麦滋林) Smectite(思密达)

misoprostol Sucralfate Bismuch, etc.

Drugs used for peptic ulcers Misoprostol 米索前列醇 A prostaglandin E analogues

Drugs used for peptic ulcers Misoprostol 米索前列醇 1. Pharmacological effects Inhibiting gastric acid secretion Promoting mucus and HCO3- secretion, and mucosal repair 2. Clinical uses Only approved for the prevention of NSAIDs-induced gastric Ulcer. 3. Adverse effects Side effects (13%):abdominal pain, diarrhea, nausea, headache, etc. Contraindicated in pregnancy women (Abortifacient 堕胎 property) Misoprostol has both acid inhibitory and mucosal protective properties. it binds to a prostaglandin receptor on parietal cells, reducing histamine-stimulated cAMP production and causing modest acid inhibition Peptic ulcers develop in approximately 10–20% of patients who receive long-term NSAID therapy Diarrhea and cramping abdominal pain occurs in 10–20% of patients. misoprostol stimulates uterine contractions (

Sucralfate Drugs used for peptic ulcers A sulfated disaccharide（二糖） complex of aluminum hydroxide

Sucralfate Drugs used for peptic ulcers 1. Pharmacological effects 1) Binding to mucosal surface and forms a protective barrier 2) Enhancing cell restitution and re-epithelization. 3) Weakly inhibiting H.Pylory growth. 4) Promote PGE2 production 5) Binding to pepsin and then reduce its activity 2. Clinical uses and Adminstration peptic ulcers, but with the advent of more effective agents (proton pump inhibitors); reflux esophagitis; mucosa impairment. Take sucralfate 1 hour before meals Four times a day before meals and at bedtime 3. Adverse effects Constipation occurs in 2% due to the aluminum salt, not together with alkaline agents Sucralfate is a salt of sucrose complexed to sulfated aluminum hydroxide. the negatively charged sucrose sulfate binds to positively charged proteins in the base of ulcers or erosion, forming a physical barrier that restricts further caustic damage and stimulates mucosal prostaglandin and bicarbonate secretion. It may also bind epithelial growth factor and fibroblast growth factor, enhancing mucosalrepair a small amount of aluminum is absorbed, it should not be used for prolonged periods in patients with renal insufficiency.

Bismuth Compounds Drugs used for peptic ulcers Colloidal bismuth subcitrate (CBS, 胶体次枸橼酸铋) Bismuth subslicylate 1. Pharmacological effects 1) Probably coats ulcers and erosions, creating a protective layer against acid and pepsin 2) Inhibit pepsin activity, stimulate prostaglandin, mucus, and bicarbonate secretion 3) Have direct antimicrobial activity against H pylori

Bismuth Compounds Drugs used for peptic ulcers 2. Clinical uses 1) Treatment of dyspepsia, peptic ulcer, chronic gastritis. 2) Used in multidrug regimens for the eradication of H pylori infection. 3. Adverse effects Causes blackening of the stool, which may be confused with gastrointestinal bleeding Bismuth toxicity resulting in encephalopathy (ataxia, headaches, confusion, seizures). 1.bismuth subsalicylate, bismuth subcitrate and bismuth dinitrate are also available. 2. All bismuth formulations have an excellent safety profile. 3. Bismuth agents should be used for only short periods and should be avoided in patients with renal insufficiency.

Smectite(蒙脱石) Drugs used for peptic ulcers Bind to the glycoprotein in the mucus to increase its coverage ability, enhancing cell restitution, antimicrobial activity against H pylori. 2) Use for acute or chronic diarrhea and ulcer.

Ⅳ. Antimicrobial(anti-Hp) drugs Drugs used for peptic ulcers Ⅳ. Antimicrobial(anti-Hp) drugs 1. Anti-ulcer drugs: H+-K+-ATPase inhibitors; bismuch(铋剂); sulralfate(硫糖铝), etc. Weaker, combined with antimicrobial drugs. 2. Antimicrobial drugs: Metronidazole(甲硝唑); Amoxicillin(阿莫西林); Tetracycline(四环素); Gentamicin (庆大霉素); Clarithromycin(克拉霉素), etc.

misoprostol Sucralfate Bismuch, etc.

新进展 我国HP感染率总体上仍然很高，成人感染率在 40-60%。 --第四次全国幽门螺杆菌感染处理共识报告（2012年） 我国HP感染率总体上仍然很高，成人感染率在 40-60%。 推荐用于根除治疗的6种抗菌药物中，甲硝唑耐药率已达到60%-70%，克拉霉素达20%--38%，左氧氟沙星达到30%--38%，耐药显著影响根除率。 羟氨苄青霉素、呋喃唑酮和四环素的耐药率仍很低（1%-5%） 。 因此标准三联疗法（PPI+克拉霉素+羟氨苄) 或（PPI+克拉霉素+甲硝唑）根除率已低于或远低于80%。 共识： 推荐四联： PPI+铋剂+2种抗菌药物 抗菌药物组成： 羟氨苄青霉素+克拉霉素 羟氨苄青霉素+左氧氟沙星 羟氨苄青霉素+呋喃唑酮 四环素+甲哨唑或呋喃唑酮

新进展 青霉素过敏者推荐的抗菌药物组成方案： 疗程： 10d--14d，放弃7d方案。 克拉霉素+左氧氟沙星 克拉霉素+呋喃唑酮 四环素+甲硝唑或呋喃唑酮 克拉霉素+甲硝唑 疗程： 10d--14d，放弃7d方案。

Gastrointestinal drugs Part2 Modulators of gastrointestinal functions

Abnormalities of gastrointestinal functions Modulators of gastrointestinal functions Abnormalities of gastrointestinal functions Nausea and vomiting Constipation Diarrhea

Contents Ⅰ. Promoting digestive drug(助消化药) Ⅱ. Antiemetic and prokinetic drugs 1. antiemetic drugs(止吐药) 2. prokinetic drugs(胃动力药) Ⅲ. Drugs for treatment of diarrhea 1. antimotility drugs(抗蠕动药) 2. astringents(收敛药) 3. absorbants(吸附药) Ⅳ. Laxatives 1. contact(stimulant) laxatives 2. osmotic laxatives 3. faecal softners(emollients)

Ⅰ. Promoting digestive drug Pepsin(胃蛋白酶) Pancreatin(胰酶) Modulators of gastrointestinal functions Ⅰ. Promoting digestive drug Pepsin(胃蛋白酶) Pancreatin(胰酶) Lactasin(乳酶生, Biofermin, 表飞鸣) etc.

Ⅱ. Antiemetic and prokinetic drugs 1. Antiemetic drugs(止吐药) Modulators of gastrointestinal functions Ⅱ. Antiemetic and prokinetic drugs 1. Antiemetic drugs(止吐药) H1 receptor antagonists(H1受体阻断药): Diphenhydramine(苯海拉明); Dimenhydrinate(茶苯海明); Meclozine(美克洛嗪) M receptor antagonists(M受体阻断药): Scopolamine(东莨菪碱) D2 receptor antagonists(D2受体阻断药): Chlorpromazine(氯丙嗪) 5-HT3 receptor antagonists(5-HT3受体阻断药): Ondansetron(昂丹司琼) Grasetron(格拉司琼) Tropisetron(托烷司琼)

2. Prokinetic drugs(胃动力药) Modulators of gastrointestinal functions 2. Prokinetic drugs(胃动力药) Metoclopramide(甲氧氯普胺, 胃复安, 灭吐灵) D2 receptor block: antiemetic effects(CTZ), and promoting GI motility. Adverse effects: CNS reactions, extrapyra-midal effects, etc. Domperidone(多潘立酮, 吗丁啉) D2 receptor block: promoting GI motility. Adverse effects: headache, prolactin , gastric acid  Cisapride(西沙比利) 5-HT4 receptor activitor, ACh release : promoting intestinal & colon motility.

GI tract smooth muscle cells Prokinetic drugs NANC neuron Post-ganglionic primary motor neuron Cholinergic neuron GI tract smooth muscle cells

Prokinetic drugs Modulators of gastrointestinal functions Metoclopramide 甲氧氯普胺 Mechanism of action 1) Block D2 receptor, to stimulate 5-HT4 receptors and enhance coordinated transmission in cholinergic nerve plexues 2) An dopaminergic neuron antagonist in the central nervous system; at higher doses, 5-HT3 antagonist activity may also contribute to the anti-emetic effect. Clinical uses 1) Used for treatment of diabetic gastroparesis 2) Used for the prevention of nausea and vomiting associated with cancer chemotherapy or occurring post-operatively.

Metoclopramide Modulators of gastrointestinal functions Adverse effects 1) Fatigue, dizziness, faintness 2) Various extrapyramidal syndromes caused by its central anti-dopaminergic activity. Parkinsonism (reversible) tardive dyskinesia (irreversible) 3) Increased serum prolactin levels (chronic uses)

Domperidone 多潘立酮 Mechanism of action Modulators of gastrointestinal functions Domperidone 多潘立酮 Mechanism of action A peripherial dopamine antagonist, has no procholinergic Effects Clinical uses 1) Used for treatment of diabetic gastroparesis 2) Used for the prevention of nausea and vomiting induced by dyspepsia, chemotherapy, gastroesophageal reflux disease . Adverse effects Has few side effects because it can not cross the BBB Increased serum prolactin levels (6% of patients) Rare cases of prolongation of QT interval.

Ⅲ. Drugs for treatment of diarrhea (止泻药) Modulators of gastrointestinal functions Ⅲ. Drugs for treatment of diarrhea (止泻药) 1. Antimotility drugs(抗蠕动药) : agonists for  receptors in GI tract Opium preparations(阿片制剂) Diphenoxylate(地芬诺酯): CNS effects at larger doses. 2. Astringents(收敛药) : Tannalbin(鞣酸蛋白) Bismuch subsalicylate(次硅酸铋) Bismuch subcarbonate(次碳酸铋) 3. Absorbants(吸附药) : Medical charchol(药用炭, 活性炭) Agysical(矽炭银)

Anti-diarrheals 1. Antimotility drugs: Modulators of gastrointestinal functions Anti-diarrheals 1. Antimotility drugs: Mechanisms: Agonists for  receptors in GI tract (1) Opium preparation 阿片制剂 (2) Diphenoxylate 地芬诺酯 Diphenoxylate dose not cross the blood-brain-barrier as easly as most opioids do and is relatively selective for peripheral opioid receptors. Has CNS effects at larger doses) Opioids increase colonic phasic segmenting activity through inhibition of presynaptic cholinergic nerves in the submucosal and myenteric plexuses and lead to increased colonic transit time and fecal water absorption. Although all opioids have antidiarrheal effects, central nervous system effects and potential for addiction limit the usefulness of most. Loperamide is a nonprescription opioid agonist that does not cross the blood-brain barrier and has no analgesic properties or potential for addiction. Diphenoxylate is another opioid agonist that has no analgesic properties in standard doses; however, higher doses have central nervous system effects and prolonged use can lead to opioid dependence.

Loperamide 洛哌丁胺 Anti-diarrheals 1. Antimotility drugs: Modulators of gastrointestinal functions Anti-diarrheals 1. Antimotility drugs: Loperamide 洛哌丁胺 It is two to three times potent than diphenoxylate, and its action is more rapid in onset and more prolonged. Use for acute or chronic diarrhea but not induced by infection. It has less CNS or cardiovascular effects .

Ⅳ. Laxatives(泻药) Phenolphthalein(酚酞) Bisacodyl(必沙可啶) Modulators of gastrointestinal functions Ⅳ. Laxatives(泻药) 1. Stimulant laxatives(刺激性泻药) Phenolphthalein(酚酞) Bisacodyl(必沙可啶) Rhubarb(大黄)、Senna(番泻叶), etc. 2. Osmotic laxatives(渗透性泻药) Magnesium sulfate(硫酸镁); Sodium sulfate(硫酸钠); Lactulose(乳果糖); Sorbitol(山梨醇); Glycerol(甘油); Celluloses(纤维素类) 3. Faecal softners(粪便软化药, emollients) Liquid paraffin(液体石蜡)

Laxatives 1. Stimulant laxatives(刺激性泻药) Modulators of gastrointestinal functions Laxatives 1. Stimulant laxatives(刺激性泻药) Phenolphthalein 酚酞 ( No longer used because of concerns about carcigenicity) Bisacodyl 必沙可啶 (It is active after deacetylation, stimulating enteric nerves to cause colonic mass movements; increases fluid and NaCl secretion. ) Stimulant laxatives (cathartics) induce bowel movements through a number of poorly understood mechanisms. These include direct stimulation of the enteric nervous system and colonic electrolyte and fluid secretion. Phenolphthalein will react with bile or intestinal juice to form soluble salt. The soluble salt stimulates colonic peristaltic movement and inhibits the sorption of water. Bisacodyl is the silmilar to phenolphthalein in pharmacological action. Anthraquinones include rhubarb and senna which both can produce anthraquinone with the help of enteric bacteria. Anthraquinone stimulates colonic peristaltic movement

Laxatives Anthraquinones 蒽醌类（中药成分） Modulators of gastrointestinal functions Laxatives Anthraquinones 蒽醌类（中药成分） promote colon movements Cascara （鼠李皮） Senna （番泻叶） Rhubarb （大黄）

Laxatives 2. Osmotic laxatives(渗透性泻药) Modulators of gastrointestinal functions Laxatives 2. Osmotic laxatives(渗透性泻药) 1) Salt laxatives: magnesium sulfate 硫酸镁; sodium sulfate 硫酸钠； These agents contain ions that are only slowly absorbed from the intestine. These ions retain fluid in the bowel lumen and cause a large volume of fluid to enter the colon. Osmotic laxatives: Osmotic laxatives are soluble but no absorbable compounds that result in increased osmotic pressure, which inhibits the absorption of water and increases intestinal contents. magnesium sulfate : It should not be used for prolonged periods in patients with renal insufficiency due to risk of Hypermagnesemia. These hyperosmolar agents may lead to intravascular volume depletion and electrolyte fluctuations; hence they should not be used in patients who are frail, elderly, have renal insufficiency, or have significant cardiac disease. Lactulose are nonabsorbable sugars.These sugars are metabolized into lactic acid by colonic bacteria , producing increased intestinal contents. Sorbitol and glycerol have weak catharsis purgation effects. So they are suitable for the aged and childs Faecal softners : liquid paraffin lubricates fecal material, retarding water absorption from the stool. It is used to prevent and treat fecal impaction in young children and debilitated adults

Laxatives 2. Osmotic laxatives(渗透性泻药) 2) Lactulose 乳果糖; Modulators of gastrointestinal functions Laxatives 2. Osmotic laxatives(渗透性泻药) 2) Lactulose 乳果糖; In the small bowel, it is resistant to hydrolysis and has an osmotic effect. In the large intestine, lactulose is acted upon by the endogenous flora with the production of lactic acid, Lactic acid also has an osmotic effect. It is used to reduce ammonia blood levels in the prevention and treatment of hepatic encephalopathy

3. Laxatives that decrease absorption Modulators of gastrointestinal functions 3. Laxatives that decrease absorption Liquid petrolatum ( Lubricate the fecal mass, prevent excessive dehydration of the material , and may inhibit water reabsorption by coating the gut wall)

Thanks